The present invention relates to pharmaceutical compositions for regulating unitary smooth muscle polarization. The invention further relates to a kit containing at least two of the above pharmaceutical compositions.
Patent FR 2 602 678 has already described aqueous pharmaceutical compositions based on magnesium, sodium and potassium salts for regulating the local circulations, which are particularly suitable in the treatment of recurring disorders and diseases of the upper respiratory tract.
These compositions consist of an aqueous solution containing magnesium, potassium, sodium and optionally calcium salts in combination with at least one sugar and at least one amino acid.
The sugar contained in these compositions is an absorbable sugar selected from glucose, galactose and xylose, or optionally a non-absorbable sugar such as mannitol.
The amino acid contained in these compositions is selected from arginine, phenylalanine and glutamic acid.
Apart from its role in conveying the inspired air, the respiratory tract is responsible for translating and processing the airborne information arriving from the outside world. Its essential task is to free the inspired air of the inert or living particles it contains. The respiratory tract does this by deploying several barriers on its surface for neutralizing the airborne contaminants:
the mucociliary barrier PA1 the commensal micro-organism barrier PA1 the secretory IgA barrier.
However, whereas along the whole of the respiratory tract this trapping of the contaminants depends on random contact with the wall, at the rhinosinusal stage there is a dynamic structure which consists of a very dense vascular network with erectile tissue and whose variations in volume have a dual effect: to channel and precipitate the aerial contaminants onto the mobile mucociliary barrier, and to connect the sinusal surfaces to the respiratory system.
This apparatus is driven by unitary smooth muscle tissue. The unitary smooth muscles have the characteristic property of contracting spontaneously, excited only by local factors (physical factors, for example stretching, and chemical or metabolic factors). They drive the microcirculation and the mucociliary function of the respiratory mucosae. Whatever its nature, the information received modifies the membrane polarity of this muscle tissue and generates action potentials with which a contraction is associated. This automatic activity is initiated in stimulating cells (of the pacemaker type) variably located in the tissue, and propagates to all the tissue as though a single structure were involved.
This spontaneous activity, which is only modulated and not triggered by their innervation, permits local autoregulation. It is this tissue which constitutes the muscle cells of the capillary sphincters and of the arteriovenous anastomosis, the myofibrils of the secretory cells and glands and the contractile proteins of the ciliated cells. This is how this apparatus can be autoregulated by the air stream and the airborne contaminants which carry the physical information, and by local metabolic factors which carry the pharmacological information, the autonomous nervous system only coming into play for punctual actions of defense or adaptation of the mucosa.
The transduction of this information is not biochemical but biophysical: action potentials are spontaneously generated whatever the information: physical, chemical or metabolic. A contraction of the unitary smooth muscle tissue is associated with the volley of action potentials and drives the microcirculation and the mucociliary system, and this contraction is not only well synchronized but also modulated by the excitation and adapted to the excitation by virtue of the action potentials, which can vary in number, amplitude and frequency. This so-called phase contraction is the functional contraction.
It is excessive variations in the membrane polarity which will dysregulate this apparatus. Strong excitations or strong inhibitions carried by endogenous factors and (or) exogenous factors can cause the muscle membrane to break through a polarization or depolarization threshold beyond which the spontaneous generation of action potentials is abolished. A tonic contraction is then set up which is uniform and dysregulatory because it depends on passive calcium ion movements not modulated by the information.
Depending on the etiological factors, the abolition of the action potentials can in the first instance electively dysregulate the microcirculatory function or the mucociliary function and thereby create various pathogenic processes. Two are particularly important on account of their frequency and their major role in the initiation of disorders and diseases of the upper respiratory tract.
Dysregulation of the contraction of one or both capillary sphincters or the muscular tunic of the arteriovenous anastomosis causes a vasomotor disorder of variable clinical expression: in the first case, for example, this is initially a mechanical edema, but the ionic and metabolic perturbations which have been triggered generate a tissue edema.
Dysregulation of the contraction of the mucociliary contractile proteins causes hypersecretion or hyposecretion with ciliary dyskinesia. Dehydration of the mucosa, in particular, is a formidable disorder. In the absence of a mucociliary barrier, the contaminants will behave like airborne particles and, in contact with the mucosa, will either trigger an immune reaction, if they attach themselves thereto or penetrate it, or exhibit a pathogenic physical action. This action varies with the charge, mass, speed and angle of impact of the contaminants. Whether the action exhibited is mechanical, caloric or electromagnetic, it is a source of hemodynamic perturbations and non-specific inflammatory reactions, with vasomotor disorders.